Tumor necrosis factor-α triggers a cytokine cascade yielding postoperative cognitive decline

Terrando, Niccolò; Monaco, Claudia; Ma, Daqing; Foxwell, Brian M. J.; Feldmann, Marc; Maze, Mervyn

doi:10.1073/pnas.1014557107

Cited by 618 publications

(568 citation statements)

References 51 publications

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“…HMGB1 regulates neuronal and dendritic growth, and, as do TNF and IL-1, induces sickness behavior associated with fever, anorexia, withdrawal and impaired cognition. Administration of anti-TNF antibody and anti-IL-1 antibody in acute murine injury and infection models significantly improves cognitive abnormalities (12,13). Clinical studies of serum cytokine levels in severe sepsis survivors indicate that HMGB1 levels are increased significantly at the time of hospital discharge, whereas TNF and IL-1 levels are not (8,14).…”

Section: Hmgb1 Mediates Cognitive Impairment In Sepsis Survivorsmentioning

confidence: 99%

HMGB1 Mediates Cognitive Impairment in Sepsis Survivors

Chavan

Huerta

Robbiati

et al. 2012

Mol Med

173

160

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Severe sepsis, a syndrome that complicates infection and injury, affects 750,000 annually in the United States. The acute mortality rate is approximately 30%, but, strikingly, sepsis survivors have a significant disability burden: up to 25% of survivors are cognitively and physically impaired. To investigate the mechanisms underlying persistent cognitive impairment in sepsis survivors, here we developed a murine model of severe sepsis survivors following cecal ligation and puncture (CLP) to study cognitive impairments. We observed that serum levels of high mobility group box 1 (HMGB1), a critical mediator of acute sepsis pathophysiology, are increased in sepsis survivors. Significantly, these levels remain elevated for at least 4 wks after CLP . Sepsis survivors develop significant, persistent impairments in learning and memory, and anatomic changes in the hippocampus associated with a loss of synaptic plasticity. Administration of neutralizing anti-HMGB1 antibody to survivors, beginning 1 wk after onset of peritonitis, significantly improved memory impairments and brain pathology. Administration of recombinant HMGB1 to naïve mice recapitulated the memory impairments. Together, these findings indicate that elevated HMGB1 levels mediate cognitive decline in sepsis survivors, and suggest that it may be possible to prevent or reverse cognitive impairments in sepsis survivors by administration of anti-HMGB1 antibodies.

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Section: Hmgb1 Mediates Cognitive Impairment In Sepsis Survivorsmentioning

confidence: 99%

HMGB1 Mediates Cognitive Impairment in Sepsis Survivors

Chavan

Huerta

Robbiati

et al. 2012

Mol Med

173

160

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“…High serum levels of TNF-α are associated with neuropsychiatric disorders such as major depressive disorder (11,54), abnormalities of brain development including autism (55), autoimmune diseases such as multiple sclerosis and rheumatoid arthritis (56), postoperative cognitive decline (57), and neurodegenerative diseases such as Alzheimer's disease (58). High serum cytokine levels in patients immunized with lipopolysaccharide or Salmonella typhi vaccination has been associated with cognitive changes including mental confusion (17) and depressive symptoms including psychomotor retardation (11,59).…”

Section: Discussionmentioning

confidence: 99%

Peripheral elevation of TNF-α leads to early synaptic abnormalities in the mouse somatosensory cortex in experimental autoimmune encephalomyelitis

Yang

Parkhurst

Hayes

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Sensory abnormalities such as numbness and paresthesias are often the earliest symptoms in neuroinflammatory diseases including multiple sclerosis. The increased production of various cytokines occurs in the early stages of neuroinflammation and could have detrimental effects on the central nervous system, thereby contributing to sensory and cognitive deficits. However, it remains unknown whether and when elevation of cytokines causes changes in brain structure and function under inflammatory conditions. To address this question, we used a mouse model for experimental autoimmune encephalomyelitis (EAE) to examine the effect of inflammation and cytokine elevation on synaptic connections in the primary somatosensory cortex. Using in vivo two-photon microscopy, we found that the elimination and formation rates of dendritic spines and axonal boutons increased within 7 d of EAE induction-several days before the onset of paralysis-and continued to rise during the course of the disease. This synaptic instability occurred before T-cell infiltration and microglial activation in the central nervous system and was in conjunction with peripheral, but not central, production of TNF-α. Peripheral administration of a soluble TNF inhibitor prevented abnormal turnover of dendritic spines and axonal boutons in presymptomatic EAE mice. These findings indicate that peripheral production of TNF-α is a key mediator of synaptic instability in the primary somatosensory cortex and may contribute to sensory and cognitive deficits seen in autoimmune diseases.

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“…One of the earliest changes during sepsis, due to pro-inflammatory cytokines, is microglial activation which in turn leads to neuronal loss. Oxidative stress, mitochondrial dysfunction with mitochondrial-mediated apoptosis, impaired cerebral perfusion and persistent hyperglycaemia are other important mechanisms that may induce brain dysfunction [12][13][14][15][16][17][18][19] . Neurotransmitter imbalance, especially between dopaminergic and cholinergic neurotransmission, seems to play a significant role and there are other significant neurotransmitters (beta-adrenergic substances, gamma-aminobutyric acid, serotonergic agents) whose alterations affect the development of delirium 1,11 .…”

Section: Sepsismentioning

confidence: 99%

“…It may be the next explanation of the small incidence of delirium in our study compared with the results of some other studies. It is widely accepted that one of the most common causes of delirium in medical intensive care units is sepsis [11][12][13][14][15] . One of the earliest changes during sepsis, due to pro-inflammatory cytokines, is microglial activation which in turn leads to neuronal loss.…”

Section: Sepsismentioning

confidence: 99%

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Incidence and risk factors for delirium development in ICU patients - a prospective observational study

Káňová¹,

Sklienka²,

Kula³

et al. 2017

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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a Background and Aims. Delirium is an acute brain dysfunction and a frequent complication in critically ill patients. When present it significantly worsens the prognosis of patients. The aim of this study was to evaluate the incidence of delirium and risk factors for delirium in a mixed group of trauma, medical and surgical ICU patients. Methods. A prospective observational study was conducted in one of the six-bed Intensive Care Units of the University Hospital Ostrava in the Czech Republic during a 12-month period. We evaluated the incidence of delirium and its predisposing and precipitating risk factors. All patients were assessed daily using the Confusion Assessment Method for the ICU (CAM-ICU). Results and Conclusions. Of the total of 332 patients with a median APACHE II (the Acute Physiology and Chronic Health Evaluation) score of 12, who were evaluated for delirium, 48 could not be assessed using CAM-ICU (47 due to prolonged coma, 1 due to language barriers). The incidence of delirium was 26.1%, with trauma and medical patients being more likely to develop delirium than surgical patients. Risk of delirium was significantly associated with age ≥ 65 years, and alcohol abuse in their anamnesis, with APACHE II score on admission, and with the use of sedatives and/or vasopressors. Delirious patients who remained in the ICU for a prolonged period showed a greater need for ventilator support and had a greater ICU-mortality.

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Tumor necrosis factor-α triggers a cytokine cascade yielding postoperative cognitive decline

Cited by 618 publications

References 51 publications

HMGB1 Mediates Cognitive Impairment in Sepsis Survivors

HMGB1 Mediates Cognitive Impairment in Sepsis Survivors

Peripheral elevation of TNF-α leads to early synaptic abnormalities in the mouse somatosensory cortex in experimental autoimmune encephalomyelitis

Incidence and risk factors for delirium development in ICU patients - a prospective observational study

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